Toxicokinetics and postmortem redistribution of amantadine in rats

Back to news list

Source: Frontiers Medicine

Original: https://www.frontiersin.org/articles/10.3389/fmed.2026.1783529...

Published: 2026-02-27T00:00:00Z

The study investigated the toxicokinetics and postmortem redistribution of amantadine in male rats, which is an antiviral and antiparkinsonian drug with a narrow therapeutic window and a risk of severe intoxication. Rats received oral doses of 42 mg/kg (low), 450 mg/kg (LD50) and 900 mg/kg (2 x LD50), concentrations were measured in blood and nine tissues over 96 hours for toxicokinetics and postmortem storage at 4°C and 20°C. Amantadine was rapidly absorbed, widely distributed with tissue-specific heterogeneity - highest exposure in liver and kidney, limited accumulation in brain and testes. Postmortem redistribution was significant, dependent on dose, postmortem interval, and temperature; blood concentrations were unstable, while liver and spleen had higher and more persistent values. Concentration ratios such as liver-leg quality or spleen-brain showed consistent dose-dependent trends. The findings highlight the instability of postmortem blood concentrations and recommend the use of tissue and inter-tissue ratios for better toxicological interpretation of amantadine intoxication.